1. Field of the Invention
This invention relates to a new compound of (vinylphenyl)phenylmethane which is represented by the formula (I) and a new method for producing .alpha.-(3-benzoylphenyl)propionic acid by using the above compound as an intermediate.
The compound prepared by the method of the present invention is .alpha.-(3-benzoylphenyl)propionic acid (tradename: ketoprofen) which is represented by the following formula (III) and which is used as a medicine for the relief of pain, fever and inflammation. ##STR1##
2. Description of Prior Art
In connection with the ketoprofen, various preparation methods have been hitherto proposed. Among them, typical ones are described briefly in the following.
(1) 3-Methylbenzophenone is subjected to bromination to produce 3-bromomethylbenzophenone, which is then reacted with potassium cyanide to produce 3-cyanomethylbenzophenone. This 3-cyanomethylbenzophenone is then methylated and methyl iodide in the presence of a base. The process is further followed by alkali hydrolysis to obtain ketoprofen (Japanese Laid-Open Patent Publication No. 51-115452). ##STR2##
(2) 3-Chlorobenzoic acid is reacted with propionitrile in the presence of a strong base to form .alpha.-(3-carboxylphenyl)propionitrile, which is then reacted with thionyl chloride to obtain .alpha.-(3-chlorocarbonylphenyl)propionitrile. This compound is further reacted with benzene in the presence of aluminum chloride catalyst (Friedel-Crafts reaction) to obtain 3-(1-cyanoethyl)benzophenone and it is subjected to alkali hydrolysis to produce ketoprofen (Japanese Laid-Open Patent Publication No. 52-8301). ##STR3##
(3) Friedel-Crafts alkylation is carried out with benzophenone and diethyl sulfate in the presence of aluminum chloride to form 3-ethylbenzophenone. It is then subjected to bromination using N-bromosuccinimide to produce 3-(1-bromoethyl)benzophenone, which is then subjected to alkali hydrolysis to obtain 3-(1-hydroxyethyl)benzophenone. This compound is further reacted with carbon monoxide to obtain ketoprofen (Spanish Patent No. 452,500). ##STR4##
It should be noted, however, that the above method (1) is undesirable as an industrial process because the toxic potassium cyanide is used when 3-cyanomethylbenzophenone is synthesized. The other methods (2) and (3) suffer from the defect of low yield in the synthesis of (3-carboxylphenyl)propionitrile in the former method (2) and in the synthesis of 3-ethylbenzophenone in the latter method (3). Accordingly, they are not satisfactory as industrial production processes. In addition, the method (3) has another disadvantage in that the step to convert ethyl moiety of 3-ethylbenzophenone into propionic acid is difficult and low in yield, which fact is common to processes using 3-ethylbenzophenone.